Bupropion hydrochloride

Uses and Indications

Bupropion hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD).

There are no teratogenic or nonteratogenic effects associated with the use of this medication.

Dosage and Administration

The recommended starting dose for the medication is 200 mg per day, administered as 100 mg twice daily. To minimize the risk of seizures, it is advised to increase the dose gradually. After an initial period of 3 days, the dose may be increased to 300 mg per day, given as 100 mg three times daily, ensuring that there is an interval of at least 6 hours between doses. The usual target dose is 300 mg per day, maintained as 100 mg three times daily.

The maximum allowable dose is 450 mg per day, which can be administered as 150 mg three times daily. It is important for healthcare professionals to periodically reassess the patient's dose and the necessity for ongoing maintenance treatment.

For patients with moderate to severe hepatic impairment, the recommended dose is 75 mg once daily. In cases of mild hepatic impairment, consideration should be given to reducing the dose and/or frequency of administration. Additionally, for patients with renal impairment, a reduction in dose and/or frequency may also be warranted.

Contraindications

Use of bupropion hydrochloride tablets is contraindicated in the following situations:

• Patients with a seizure disorder, due to the increased risk of seizures.

• Individuals with a current or prior diagnosis of bulimia or anorexia nervosa, as these conditions may heighten the risk of seizures.

• Patients who have abruptly discontinued alcohol, benzodiazepines, barbiturates, or antiepileptic drugs, as this may also increase seizure risk.

• Co-administration with Monoamine Oxidase Inhibitors (MAOIs) intended for psychiatric disorders is contraindicated. Bupropion hydrochloride tablets should not be used concurrently with MAOIs or within 14 days of discontinuing either treatment. Additionally, bupropion hydrochloride tablets should not be initiated in patients receiving linezolid or intravenous methylene blue.

• Individuals with known hypersensitivity to bupropion or any other components of bupropion hydrochloride tablets.

Warnings and Precautions

The use of bupropion hydrochloride tablets necessitates careful consideration of several warnings and precautions to ensure patient safety.

Increased Risk of Suicidal Thoughts and Behaviors There is an increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants, including bupropion. Healthcare professionals should closely monitor these patients for any worsening of symptoms or emergence of suicidal thoughts and behaviors.

Neuropsychiatric Adverse Events During Smoking Cessation Postmarketing reports have indicated serious neuropsychiatric adverse events associated with bupropion during smoking cessation. These events may include mood changes (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, as well as suicidal ideation, suicide attempts, and completed suicides. Patients attempting to quit smoking should be observed for these symptoms, and if they occur, bupropion should be discontinued immediately, and the patient should contact a healthcare provider.

Seizure Risk The risk of seizures is dose-related. To minimize this risk, it is recommended to gradually increase the dose and limit the daily dose to a maximum of 450 mg. If a seizure occurs, bupropion should be discontinued.

Hypertension Bupropion hydrochloride tablets can elevate blood pressure. It is essential to monitor blood pressure prior to initiating treatment and periodically throughout the treatment course.

Activation of Mania/Hypomania Patients should be screened for bipolar disorder prior to treatment initiation. Continuous monitoring for symptoms of mania or hypomania is advised during treatment.

Psychosis and Other Neuropsychiatric Reactions Patients should be instructed to contact a healthcare professional if they experience any neuropsychiatric reactions, including psychosis.

Angle-Closure Glaucoma There have been reports of angle-closure glaucoma in patients with untreated anatomically narrow angles who are treated with antidepressants.

Monitoring Parameters Healthcare professionals are advised to monitor blood pressure before starting treatment and periodically during the course of therapy to ensure patient safety.

Emergency Instructions Patients should be instructed to discontinue bupropion and seek immediate medical assistance if they experience any neuropsychiatric adverse events.

Discontinuation Instructions Patients must be advised to stop taking bupropion and contact their healthcare provider if they experience neuropsychiatric adverse events or if a seizure occurs.

Side Effects

Most common adverse reactions observed in patients include agitation, dry mouth, constipation, headache or migraine, nausea or vomiting, dizziness, excessive sweating, tremor, insomnia, blurred vision, tachycardia, confusion, rash, hostility, cardiac arrhythmias, and auditory disturbances.

Patients taking antidepressants, including bupropion hydrochloride, are at an increased risk of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults. It is essential to monitor these patients for any worsening or emergence of suicidal thoughts and behaviors.

During smoking cessation, neuropsychiatric adverse events may occur, including changes in mood (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempts, and completed suicides. Patients should be advised to contact a healthcare professional if they experience any of these reactions.

There is a dose-related risk of seizures associated with bupropion hydrochloride. To minimize this risk, it is recommended to gradually increase the dose and limit the daily dose to 450 mg. Discontinuation of the medication is advised if a seizure occurs. Additionally, bupropion hydrochloride tablets can increase blood pressure; therefore, blood pressure should be monitored before and periodically during treatment.

Patients with a history of bipolar disorder should be screened and monitored for activation of mania or hypomania. Psychosis and other neuropsychiatric reactions have been reported, and patients should be instructed to seek medical advice if such reactions occur.

Angle-closure glaucoma has been reported in patients with untreated anatomically narrow angles who are treated with antidepressants.

Other important considerations include the presence of a seizure disorder, current or prior diagnosis of bulimia or anorexia nervosa, and the abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. Bupropion hydrochloride should not be used in conjunction with monoamine oxidase inhibitors (MAOIs) intended for psychiatric disorders or within 14 days of stopping treatment with either bupropion hydrochloride or an MAOI.

In cases of overdosage, seizures have been reported in approximately one-third of all cases. Other serious reactions associated with bupropion overdose include hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes (including conduction disturbances and arrhythmias), clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure. Deaths have been reported in patients who ingested large doses of bupropion, often preceded by multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest.

Drug Interactions

Coadministration of bupropion with certain drug classes may lead to significant interactions that require careful consideration of dosage adjustments and monitoring.

CYP2B6 Inducers When bupropion is administered alongside CYP2B6 inducers such as ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin, an increase in bupropion dosage may be necessary based on clinical response. However, the dosage should not exceed the maximum recommended limit.

CYP2D6 Substrates Bupropion is a known inhibitor of CYP2D6 and may elevate the plasma concentrations of drugs metabolized by this enzyme. This includes various antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide). A dose reduction of these medications should be considered when used concurrently with bupropion.

Digoxin Bupropion may decrease plasma levels of digoxin. It is advisable to monitor digoxin levels closely in patients receiving both medications.

Drugs Lowering Seizure Threshold Caution is warranted when prescribing bupropion in conjunction with drugs that lower the seizure threshold, as this combination may increase the risk of seizures.

Dopaminergic Drugs The concomitant use of bupropion with dopaminergic agents such as levodopa and amantadine may lead to central nervous system (CNS) toxicity. Monitoring for signs of CNS effects is recommended.

Monoamine Oxidase Inhibitors (MAOIs) The use of bupropion alongside MAOIs can heighten the risk of hypertensive reactions. Close monitoring is essential when these agents are used together.

Drug-Laboratory Test Interactions Bupropion hydrochloride tablets may cause false-positive results in urine tests for amphetamines. This potential interaction should be communicated to healthcare providers conducting such tests.

Packaging & NDC

The table below lists all NDC Code configurations of Bupropion Hydrochloride, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Antidepressants have been associated with an increased risk of suicidal thoughts and behaviors in pediatric patients, specifically in children and adolescents under the age of 18, as demonstrated in pooled analyses of short-term placebo-controlled trials. While no suicides were reported in any of the pediatric trials, it is crucial for healthcare providers to monitor these patients closely for any worsening of symptoms or the emergence of suicidal thoughts and behaviors upon initiation of antidepressant therapy.

Families and caregivers play a vital role in the management of pediatric patients on antidepressants. They should be advised to maintain close observation and communication with the prescriber regarding any changes in the patient's condition. It is important for them to monitor for signs of agitation, irritability, unusual changes in behavior, and any indications of suicidality, reporting these symptoms immediately to healthcare providers.

Geriatric Use

Elderly patients, defined as those aged 65 and older, may experience a reduction in the risk of suicidal thoughts and behaviors when treated with antidepressants, as evidenced by pooled analyses of placebo-controlled trials involving over 77,000 subjects. These trials indicated that while there is an increased risk of suicidal thoughts and behavior in children, adolescents, and young adults, this risk does not extend to individuals over the age of 24.

It is essential for healthcare providers to monitor elderly patients closely for any signs of clinical worsening or the emergence of suicidal thoughts and behaviors, particularly during the initial months of treatment or when there are changes in dosage. Families and caregivers should be advised to maintain vigilant observation and to communicate any concerns with the prescriber.

All patients receiving antidepressant therapy, including geriatric patients, should be appropriately monitored for unusual changes in behavior and suicidality. This monitoring is particularly critical during the early stages of treatment and during any adjustments to the dosage, whether increases or decreases.

Pregnancy

There is no specific information available regarding the use of this medication during pregnancy, including safety concerns, dosage modifications, or special precautions that should be taken. Healthcare professionals are advised to consider the lack of data when prescribing this medication to pregnant patients and to weigh the potential risks and benefits. Women of childbearing potential should be counseled on the absence of established safety information and the importance of discussing any potential pregnancy with their healthcare provider.

Lactation

Data from published literature report the presence of bupropion and its metabolites in human milk. In a lactation study involving 10 women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure, assuming a daily consumption of 150 mL/kg, was found to be 2% of the maternal weight-adjusted dose.

There are no data available regarding the effects of bupropion or its metabolites on milk production. Limited data from postmarketing reports have not identified a clear association of adverse reactions in breastfed infants; however, it is important to note that postmarketing reports have described seizures in breastfed infants, although the relationship between bupropion exposure and these seizures remains unclear.

The developmental and health benefits of breastfeeding should be weighed against the mother’s clinical need for bupropion hydrochloride tablets and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Renal Impairment

There are no specific dosing adjustments, monitoring requirements, or precautions indicated for patients with renal impairment. The prescribing information does not provide details regarding the management of patients with reduced kidney function. Healthcare professionals should consider this lack of information when prescribing and monitoring treatment in individuals with renal impairment.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

Overdoses of bupropion have been documented, with instances involving doses of 30 grams or more. In approximately one-third of these cases, seizures were reported as a significant adverse effect. Other serious reactions associated with bupropion overdoses include hallucinations, loss of consciousness, alterations in mental status, and cardiovascular disturbances such as sinus tachycardia and ECG changes, which may manifest as conduction disturbances, including QRS prolongation or arrhythmias. Neuromuscular symptoms such as clonus, myoclonus, and hyperreflexia have also been observed.

In more severe cases, particularly when bupropion is involved in multiple drug overdoses, additional complications such as fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported. While the majority of patients have recovered without lasting effects, there have been fatalities associated with bupropion overdoses, particularly in those who ingested large quantities of the drug. In these cases, multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest were noted prior to death.

Healthcare professionals are advised to monitor patients closely for the aforementioned symptoms in the event of a suspected overdose. Immediate medical intervention may be necessary, and supportive care should be initiated as required.

Nonclinical Toxicology

There is no information available regarding teratogenic effects associated with bupropion.

Non-teratogenic effects were observed in studies where male and female rats were administered oral doses of bupropion up to 300 mg/kg/day, which is approximately six times the maximum recommended human dose (MRHD) on a mg/m² basis. These studies indicated no adverse effects on fertility, reproduction, or the growth and development of male or female offspring. However, doses of 200 mg/kg/day or greater, approximately four times the MRHD on a mg/m² basis, resulted in transient ataxia or behavioral changes in adult female rats.

Lifetime carcinogenicity studies conducted in rats and mice evaluated bupropion at doses up to 300 mg/kg/day and 150 mg/kg/day, respectively, corresponding to approximately six and two times the MRHD on a mg/m² basis. In the rat study, an increase in nodular proliferative lesions of the liver was noted at doses ranging from 100 to 300 mg/kg/day, which is approximately two to six times the MRHD on a mg/m² basis; lower doses were not assessed. The potential for these lesions to serve as precursors to liver neoplasms remains unresolved. Conversely, similar liver lesions were not observed in the mouse study, and no increase in malignant tumors of the liver or other organs was detected in either study.

Bupropion demonstrated a positive response in the Ames bacterial mutagenicity assay, with a mutation rate that was two to three times higher than the control in two of five strains tested. Additionally, an increase in chromosomal aberrations was reported in one of three in vivo rat bone marrow cytogenetic studies.

Postmarketing Experience

During postapproval use of bupropion hydrochloride tablets, the following adverse reactions have been identified that are not described elsewhere in the labeling. These reactions have been reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body (General): Reports include arthralgia, myalgia, and fever accompanied by rash and other symptoms suggestive of delayed hypersensitivity, which may resemble serum sickness.

Cardiovascular: Adverse events such as hypertension (including severe cases), orthostatic hypotension, third-degree heart block, and Brugada pattern/syndrome have been noted.

Endocrine: Instances of hyponatremia, syndrome of inappropriate antidiuretic hormone secretion, hyperglycemia, and hypoglycemia have been reported.

Gastrointestinal: Cases of esophagitis and hepatitis have been documented.

Hemic and Lymphatic: Reports of ecchymosis, leukocytosis, leukopenia, and thrombocytopenia have been received. Altered prothrombin time (PT) and/or international normalized ratio (INR), infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin.

Musculoskeletal: Adverse reactions include muscle rigidity, fever, rhabdomyolysis, and muscle weakness.

Nervous System: Reports of aggression, coma, completed suicide, delirium, dream abnormalities, paranoid ideation, paresthesia, parkinsonism, restlessness, suicide attempts, unmasking of tardive dyskinesia, and aseptic meningitis have been noted.

Skin and Subcutaneous Tissue Disorders: Serious skin reactions such as Stevens-Johnson syndrome, angioedema, exfoliative dermatitis, urticaria, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported.

Special Senses: Instances of tinnitus and increased intraocular pressure have also been documented.

Patient Counseling

Healthcare providers should inform patients that the use of antidepressants is associated with an increased risk of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults during short-term trials. It is essential to monitor all patients who are initiated on antidepressant therapy closely for any signs of clinical worsening, as well as the emergence of suicidal thoughts and behaviors.

Providers should advise families and caregivers about the importance of maintaining close observation of the patient and ensuring open lines of communication with the prescriber. This vigilance is crucial, especially during the initial months of treatment or when there are changes in dosage, whether increases or decreases.

Additionally, healthcare providers should alert families and caregivers of patients being treated for major depressive disorder (MDD) or other indications to be particularly watchful for symptoms such as agitation, irritability, and any unusual changes in behavior. They should be instructed to report these symptoms immediately to healthcare providers to ensure timely intervention and support.

Storage and Handling

The product is supplied in a tight, light-resistant container to ensure its integrity. It should be stored at a temperature range of 20ºC to 25ºC (68ºF to 77ºF), with permissible excursions between 15ºC and 30ºC (59ºF to 86ºF) as defined by USP Controlled Room Temperature guidelines. Additionally, it is essential to protect the product from moisture to maintain its quality and efficacy.

Additional Clinical Information

Bupropion hydrochloride tablets should be administered whole, without crushing, dividing, or chewing, and can be taken with or without food. Clinicians are advised to counsel patients, families, and caregivers on the importance of monitoring for the emergence of suicidal thoughts and behaviors. Immediate consultation with a healthcare provider is recommended if patients exhibit agitation, changes in mood or behavior, or develop suicidal ideation.

Postmarketing experience has revealed various adverse effects associated with bupropion, including arthralgia, myalgia, fever with rash, and symptoms indicative of delayed hypersensitivity. Clinicians should be aware of potential severe hypertension, orthostatic hypotension, and cardiac issues such as third-degree heart block and Brugada syndrome. Other reported effects include hyponatremia, hyperglycemia, esophagitis, and hepatitis. Hematological changes such as leukocytosis, leukopenia, and thrombocytopenia have been noted, particularly when bupropion is coadministered with warfarin. Neurological and psychiatric effects, including aggression, delirium, and unmasking of tardive dyskinesia, have also been documented, alongside serious skin reactions like Stevens-Johnson syndrome and DRESS. Additionally, tinnitus and increased intraocular pressure have been reported.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Bupropion Hydrochloride as submitted by Apotex Corp. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)